Figure 4. A prediction of plasma and effect-compartment concentrations (C (eff)) of morphine and M6G after 10 doses of 90 mg morphine at the 12-h interval, based on published keOvalues (t1/2,keO = 16.7 min for morphine, and 20.3 h for M6G; keO= In(2)/t1/2,keO [20]). The predicted plasma and effect-compartment concentrations of M6G in healthy persons are shown at the top and those in patients with renal failure M6G clearance 10.6 ml/min [22]are shown at the bottom. Note the different scaling of the ordinates (factor 10). In healthy volunteers, neither morphine nor M6G are expected to accumulate in plasma. In contrast, M6G but not morphine is predicted to accumulate in the effect compartment. In patients with renal failure, the reduced M6G clearance leads to an accumulation of M6G in both plasma and the effect compartment. Because renal excretion plays a minor role for morphine clearance, plasma and effect-compartment concentrations of morphine probably will not be affected in renal failure.